Mitochondrial Morphology Controls Hematopoietic Stem Cell Self-Renewal and Confers Them Divisional Memory

Regulation of hematopoietic stem cell self-renewal.

Every day, billions of new blood cells are produced in the body, each one derived from a hematopoietic stem cell (HSC). Because most mature blood stem cells have a limited life span, the ability of HSCs to perpetuate themselves through self-renewal and generate new blood cells for the lifetime of an organism is critical to sustaining life. A key problem in hematopoietic stem cell biology is how...

Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitors.

A key question concerns the mechanisms that determine temporal identity in stem cells. Fetal hematopoietic stem cells (HSCs) differ from adult HSCs in terms of gene expression profile, surface marker expression, differentiation, and self-renewal capacity. We previously showed that the transcription factor SOX17 is expressed by fetal, but not adult, HSCs and is required for the maintenance of fe...

Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through direct interactions with JAK2.

In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls HSC homeostasis and self-renewal. Under steady-state conditions, mice lacking the inhibitory adaptor protein Lnk harbor an expanded HSC pool with enhanced self-renewal. We found that HSCs from Lnk-/...

Networks Establishing Hematopoietic Stem Cell Multipotency and Self-Renewal

Deterministic regulation of hematopoietic stem cell self-renewal and differentiation.

Most current theories assume that self-renewal and differentiation of hematolymphoid stem cells (HSCs) is randomly regulated by intrinsic and environmental influences. A direct corollary of these tenets is that self-renewal will continuously generate functionally heterogeneous daughter HSCs. Decisions about self-renewal versus commitment are made by individual, single HSCs and, thus, require ex...